| Objective:Our previous study found that modified jejunoileal bypass(side-to-side jejunoileal bypass plus proximal loop ligation,SSJIBL)has significant weight loss and hypoglycemic effect.However,the specific segment of SSJIBL in treating diabetes mellitus(DM)is the best and the exact mechanism of SSJIBL in the treatment of DM is not yet clear.With side-to-side jejunoileal bypass plus proximal loop ligation(SSJIB)as a surgical model,this study systematically explored the efficacy and mechanism of SSJIBL in different segments in the treatment of non-obese diabetic rat(NODR)by treating NODR with sleeve gastrectomy(SG),duodenal-jejunal bypass(DJB),proximal small intestinal bypass(PSIB),mid small intestinal bypass(MSIB)and distal small intestinal bypass(DSIB),respectively,providing a theoretical basis for clinical application and modification of SSJIBL in the treatment of T2 DM.Methods:One hundred SPF-grade male SD rats(age,6-8 weeks;body weight,240-280 g)were selected.A model of NODR was established by a single intraperitoneal injection with 60 mg/kg streptozotocin(STZ).One week after successful establishment,60 rats were selected and randomly divided into 6 groups(SG group,DJB group,DSIB group,MSIB group,PSIB group and Sham group)with 10 rats per group.Body weight,24-hour food intake,fed blood glucose(FEG)level,fasting blood glucose(FBG),oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were detected at specific time points,respectively.Collection of related specimens after six weeks,serum electrolytes and hepatic and renal function and bile acid and blood lipid levels were determined.Serum insulin and ghrelin and leptin and glucagon-like peptide-1(GLP-1)levels were detected using enzyme linked immune-sorbent assay(ELISA).Morphological changes in postoperative liver(steatosis,fibrosis,cirrhosis,etc.)were observed by HE staining.The secretion of insulin in each group of islet ? cells was evaluated using immunofluorescence assay.Results:1.Operation time and survival rate of all the rat groups: The operation time of the Sham group was under control and thus not included in the statistical results.The operation time of the PSIB,MSIB,and DSIB groups was all lower than that of the DJB and SG groups(P < 0.05).1 rat in the SG group died 1 week after the operation;1 rat in the DSIB group died 2 weeks after the operation;1 rat in the Sham group died 2 weeks after the operation;all the other rats survived the experiment.2.Body weight and 24 h food intake: There were no significant differences(P > 0.05)in body weight between all the operation groups and the Sham group at all the time nodes.2-6 weeks after the operation,the 24 h food intakes of the PSIB,MSIB,DSIB,and DJB groups were all lower than that of the Sham group(P < 0.05),while there was no statistically significant difference in 24 h food intake between the SG group and the Sham group(P > 0.05).2-6 weeks after the operation,the 24 h food intakes of the PSIB,MSIB and DSIB groups were lower than that of the SG group(P < 0.05),while there were no statistically significant differences between the PSIB,MSIB,and DSIB groups(P > 0.05).3.FBG levels: the FBG levels of the PSIB,MSIB and DSIB groups 2-6 weeks after the operation were lower than that of the Sham group(P < 0.05).The FBG level of the SG group 2-4 weeks after the operation was lower than that of the Sham group(P < 0.05),but the difference was not statistically significant 5 weeks after the operation(P > 0.05).There was no statistically significant difference between the DJB group and the Sham group(P > 0.05).The FBG levels of the PSIB,MSIB,and DSIB groups 2-6 weeks after the operation were lower than that of the DJB group(P < 0.05),and the FBG level of the PSIB group 4-6 weeks after the operation was lower than those of the SG,MSIB and DSIB groups(P < 0.05).4.OGTT: 2 weeks after the operation,the blood glucose levels of the PSIB,MSIB,and DSIB groups 60 min after gavage were lower than that of the Sham group(P < 0.05);the blood glucose level of the SG group 90 min after gavage was lower than that of the Sham group(P < 0.05);there was no statistically significant difference between the DJB group and the Sham group(P > 0.05);there were no statistically significant differences between the PSIB,MSIB and DSIB groups and the SG group(P > 0.05);there were no statistically significant differences between the PSIB,MSIB and DSIB groups(P > 0.05).6 weeks after the operation,the blood glucose levels of the PSIB,MSIB and DSIB groups 15 min after gavage were lower than that of the Sham group(P < 0.05);there were no statistically significant differences between the DJB and SG groups and the Sham group(P > 0.05);there were no statistically significant differences between the PSIB,MSIB,DSIB,DJB and SG groups(P > 0.05).5.ITT: 2 weeks after the operation,the blood glucose decreasing rates of the PSIB,MSIB and SG groups 30 min after insulin injection were higher than that of the Sham group(P < 0.05);there were no statistically significant differences in blood glucose decreasing rate between the DSIB and DJB groups and the Sham group(P > 0.05);there were no statistically significant differences between the PSIB,MSIB,and SG groups(P > 0.05).6 weeks after the operation,the blood glucose decreasing rates of the PSIB,MSIB and SG groups 60 min after insulin injection were higher than that of the Sham group(P < 0.05);there were no statistically significant differences in blood glucose decreasing rate between the DSIB and DJB groups and the Sham group(P > 0.05);there were no statistically significant differences between the operation groups(P > 0.05).6.Liver and kidney function,and electrolyte,bile acid,and blood lipid levels: 6 weeks after the operation,there were no statistically significant differences in liver and kidney function and electrolyte level between the operation groups and the Sham(P > 0.05;the total bile acid levels of the operation groups were all lower than that of the Sham group(P < 0.05);the total bile acid level of the DSIB group was lower than those of the DJB and SG groups(P < 0.05);there were no statistically significant differences in TG,HDL,LDL and FFA levels between the operation groups and the Sham group(P > 0.05);the CHOL levels of the DSIB and MSIB groups were lower than that of the Sham group(P < 0.05).7.Serum hormone levels: 6 weeks after the operation,the insulin level of the PSIB group was higher than that of the Sham group(P < 0.05),and there were no statistically significant differences between the other operation groups and the Sham group(P > 0.05);the Ghrelin levels of the operation groups were all lower than the Sham group(P < 0.05);the GLP-1 levels of the SG,PSIB,MSIB,and DSIB groups were all higher than that of the Sham group(P < 0.05),but there was no statistically significant difference between the DJB group and the Sham group(P > 0.05);the Leptin level of the PSIB group was higher than that of the Sham group(P < 0.05),and there were no statistically significant differences between the other operation groups and the Sham group(P > 0.05);the Leptin level of the PSIB group was higher than those of the DJB,SG,MSIB,and DSIB groups(P < 0.05).8.Morphological changes of the liver: Six weeks after the operation,liver morphology was observed microscopically for all the groups through HE staining.Morphological structures of all the groups were relatively in good condition without obvious steatosis,fibrosis,liver cirrhosis,and other lesions.9.Immunofluorescence of the pancreas: the insulin immunofluorescence optical density(IOD)value of the PSIB group 6 weeks after the operation was higher than that of the Sham group(P < 0.05),and there were no statistically significant differences between the other operation groups and the Sham group(P > 0.05).Conclusions:1.All the three SSJIBL operation methods can significantly improve NODR glycometabolism,and the PSIB operation method brings about the best efficacy.2.The PSIB operation method is more effective in improving NODR glycometabolism than the DJB and SG operation methods.3.SSJIBL improves NODR glycometabolism mainly through reducing food intake and promoting GLP-1 secretion.4.Inducing proliferation of pancreatic ? cells and promoting insulin secretion may be the major mechanisms of the PSIB operation method to improve NODR glycometabolism. |
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